Container for an injectable medicament

ABSTRACT

A container for an injectable medicament can include an elongated body having a tubular-shaped sidewall extending along a longitudinal axis and having a distal end and a proximal end. The container can include an outlet at the distal end. The container can include a bung arranged inside the elongated body, sealingly engaged with the sidewall and slidable along the longitudinal axis relative to the sidewall. The container can include an interior volume to receive the injectable medicament and being confined by the sidewall, the outlet, and the bung. The container can include a measuring arrangement arranged in or on the bung. The measuring arrangement can include a signal generator configured to emit an electromagnetic measurement signal into or through the interior volume and a signal receiver configured to detect a feedback signal being indicative of an interaction of the measurement signal with at least one of the sidewall, the outlet or the interior volume.

CROSS REFERENCE TO RELATED APPLICATION

The present application is a continuation of U.S. patent applicationSer. No. 16/964,694, filed on Jul. 24, 2020, which is the national stageentry of International Patent Application No. PCT/EP2019/051553, filedon Jan. 23, 2019, and claims priority to Application No. EP 18305066.5,filed on Jan. 26, 2018, the disclosures of each of which areincorporated herein by reference in their entirety.

TECHNICAL FIELD

The present disclosure relates to measuring an interior volume of acontainer filled with a liquid substance, typically filled with aninjectable medicament. The disclosure relates to a container for aninjectable medicament. The container allows and supports a precisemeasurement of the size of an interior volume of the container occupiedby the injectable medicament. The disclosure also relates to a method ofdetermining the size of an interior volume of such a container.

BACKGROUND

Drug delivery devices for setting and dispensing a single or multipledoses of a liquid medicament are as such well-known in the art.Generally, such devices have substantially a similar purpose as that ofan ordinary syringe.

Drug delivery devices, such as pen-type injectors have to meet a numberof user-specific requirements. For instance, with patient's sufferingchronic diseases, such like diabetes, the patient may be physicallyinfirm and may also have impaired vision. Suitable drug delivery devicesespecially intended for home medication therefore need to be robust inconstruction and should be easy to use. Furthermore, manipulation andgeneral handling of the device and its components should be intelligibleand easy understandable. Such injection devices should provide settingand subsequent dispensing of a dose of a medicament of variable size.Moreover, a dose setting as well as a dose dispensing procedure must beeasy to operate and has to be unambiguous.

Typically, such devices comprise a housing or a particular cartridgeholder, adapted to receive a cartridge at least partially filled withthe medicament to be dispensed. The device further comprises a drivemechanism, usually having a displaceable piston rod to operably engagewith a bung or piston of the cartridge. By means of the drive mechanismand its piston rod, the bung or piston of the cartridge is displaceablein a distal or dispensing direction and may therefore expel a predefinedamount of the medicament via a piercing assembly, e.g. in form of aninjection needle, which is to be releasably coupled with a distal endsection of the housing of the drug delivery device.

The medicament to be dispensed by the drug delivery device is providedand contained in a multi-dose cartridge. Such cartridges typicallycomprise a vitreous barrel sealed in distal direction by means of apierceable seal and being further sealed in proximal direction by thepiston. With reusable drug delivery devices an empty cartridge isreplaceable by a filled one. In contrast to that, drug delivery devicesof disposable type are to be entirely discarded when the medicament inthe cartridge has been dispensed or used-up.

It is desirable to determine the amount of the medicament remaining in acartridge while the cartridge is arranged inside a drug delivery device.It is also desirable to determine an interior volume of the cartridgeoccupied by the liquid injectable medicament. Determination ofmeasurement of the interior volume should be rather precise, reliableand highly reproducible. It is desirable to provide a container forinjectable medicament readily equipped with volumetric measurement meansthat enables and supports electronic data processing.

SUMMARY

The present disclosure provides a container for an injectablemedicament. The container comprises an elongated body having atubular-shaped sidewall extending along a longitudinal axis (z) andhaving a distal end and a proximal end. The distal end is locatedopposite to the proximal end. The container further comprises an outletat the distal end of the elongated body. The container further comprisesa bung or a piston arranged inside the elongated body. The bung issealingly engaged with the sidewall and is slidable along thelongitudinal axis relative to the sidewall. The container furthercomprises an interior volume that may be also denoted as a fillingvolume. The interior volume or filling volume is configured to receiveand to contain the injectable medicament. The interior volume isconfined by the sidewall, by the outlet and by the bung.

The container further comprises a measuring arrangement that is arrangedin or on the bung. The measuring arrangement comprises a signalgenerator that is configured to emit a measurement signal into orthrough the interior volume. The measuring arrangement further comprisesa signal receiver configured to detect a feedback signal that isindicative of an interaction of the measurement signal with at least oneof the sidewall, the outlet or the interior volume. If the container andhence the interior volume is occupied or at least partially filled withthe injectable medicament the feedback signal may be further indicativeof an interaction of the measurement signal with the liquid medicamentcontained in the interior volume.

With the measuring arrangement in or on the bung a container with anintegrated measuring arrangement is provided. The bung of the containermay be readily equipped with the measuring arrangement. The signalgenerator and the signal receiver of the measuring arrangement areconfigured to conduct a measurement by emitting measurement signals andby detecting feedback signals in return. The measurement signal and itsinteraction with at least one of the sidewall, the outlet, the interiorvolume or the injectable medicament leads to the generation of adetectable feedback signal. The detection of the feedback signal allowsto derive at least one physical or chemical parameter of the container.In particular, the feedback signal obtainable and detectable by thesignal receiver is processable to determine at least one of the size ofthe interior volume and the longitudinal position of the bung relativeto the sidewall of the body of the container.

The integration of the signal generator and the signal receiver into oron the bung makes a separate attachment and arrangement of signalgenerator and signal receiver to the container superfluous. In order toprovide a volumetric measurement of the interior or inside volume of thecontainer it may be sufficient to provide the container with aparticular bung as described above being equipped at least with a signalgenerator and a signal receiver.

At least one of the signal generator and the signal receiver or both,the signal generator and the signal receiver may be located entirelyinside the volume or inside the bulk of the bung. The signal generatorand/or the signal receiver may be entirely enclosed by the bung. Withother examples at least one of the signal generator and the signalreceiver may be arranged at least partially inside the bung. A portionof at least one of the signal generator and the signal receiver mayflush with an outside surface of the bung. With other examples at leasta portion of at least one of the signal generator and the signalreceiver may protrude from an outside surface of the bung, e.g. from adistal face of the bung. Since the signal generator is configured toemit a measurement signal into or through the interior volume the signalgenerator may be located near a distal face of the bung pointing towardsthe distally located outlet of the container. Also, the signal receivermay be located at or close to the distal face of the bung so as to haveimmediate access to the interior volume.

With examples wherein at least one of the signal generator and thesignal receiver are entirely enclosed or embedded inside the bung eitherthe measurement signal or the feedback signal may be configured topropagate through the bung. If the signal generator is located insidethe bung at a non-zero distance from both, a distal end face and aproximal end face of the bung the measurement signal generated by thesignal generator propagates through the bung and into the interiorvolume confined by the bung. If the signal receiver is entirely embeddedinside the bung at a non-zero distance from both, the distal end faceand the proximal end face of the bung the feedback signal may alsopropagate from the interior volume into the bung in order to becomedetected by the signal receiver.

By having the signal generator and the signal receiver attached to orentirely located inside the bung even existing containers, such ascartridges for injectable medicaments and their elongated bodies can beretrofitted with a measuring arrangement. Here, an existing bung,typically configured as a rubber stopper can be exchanged by a bung asdescribed above, which bung is equipped with the measuring arrangement.

Typically, the bung comprises an elastomeric material, such as naturalor synthetic rubber. The bung may comprise a cyclic olefin polymer (COP)and/or a cyclic olefin copolymer. The bung may also comprise a polymermaterial on the basis of EPDM ethylene propylene diene monomer rubber.The measuring arrangement may be encapsulated inside the bung. Themeasuring arrangement may comprise a hermetic housing configured toaccommodate at least the signal generator and the signal receiver. Thehousing may be embedded inside the bulk of the bung. The encapsulationof at least the signal generator and the signal receiver inside thehouse of the measuring arrangement enables a multitude of different waysto manufacture the bung. For example, the housing with the signalgenerator and the signal receiver located therein may be subject to anover-molding by a bung-forming material.

With other examples the bung may comprise at least two bung componentsthat are configured to become mechanically assembled together to formthe bung. Here, the measuring arrangement can be arranged between thesebung components in order to embed the measuring arrangement inside thebung.

By embedding the measuring arrangement inside the bung the measuringarrangement is inherently protected against environmental influences orhazards. Moreover, the measuring arrangement can be concealed by andinside the bung. The embedding of the measuring arrangement inside thebung may have no influence on the outside geometry of the bung. If themeasuring arrangement is entirely embedded inside the bung and henceenclosed by the bung it is not visible from outside. In this way, themeasuring capability of the container can be effectively concealed. Thismay enable a concealed supervision or monitoring of the filling level ofthe container.

According to a further example the container comprises a processorconnected to the signal receiver. The processor may be arranged insidethe bung. The processor may belong to the measuring arrangement. Hence,the measuring arrangement may comprise the processor. The processor isconfigured to process signals obtainable from the signal receiver whenreceiving at least one feedback signal. The signal receiver is typicallyconfigured to generate an electrical signal in response to receive afeedback signal. An electrically conductive connection between theprocessor and the signal receiver enables a respective signalprocessing. Based on the signals obtainable from the signal receiver theprocessor is configured to determine at least one of a size of theinterior volume or the longitudinal position of the bung relative to thebody of the container.

The processor may comprise an integrated circuit, such as an applicationspecific integrated circuit (ASIC). The processor may be implemented asa microcontroller. The processor is at least electrically connected tothe signal receiver. The processor may be also located inside the bung.Typically, the processor is located on a printed circuit board (PCB). Atleast one of the signal generator and the signal receiver may be locatedand integrated on the same PCB. The entire measuring arrangement may beconfigured or implemented as an ASIC and may be provided on a singlecommon PCB. With other examples the processor may be located outside themeasuring arrangement. The processor may be located on a proximalsurface of the bung. It may be also located outside the bung or at apredefined non-zero distance from the bung.

The processor may be located even outside the container. The connectionbetween the processor and the signal receiver may be of wired orwireless type. When the processor is located inside or on the bung thereis provided a wired connection between the processor and the signalreceiver. With examples wherein the processor is located outside thebung and/or outside the container the processor may be connected to thesignal receiver in a wireless way.

In a further example the processor is configured to determine a size ofthe interior volume on the basis of the feedback signal obtainablethrough the signal receiver. For this, the processor may be configuredto determine a magnitude or amplitude of the feedback signal. Theprocessor may be configured to determine a time or time delay at whichthe feedback signal is detected compared to a reference signal.Alternatively, the processor may be configured to determine a phaseshift between a feedback signal and a reference signal. The processormay be further configured to compare a feedback signal with a predefinedsignal or with a previously detected feedback signal. In this way, theprocessor may be configured to monitor and to process a temporalvariation of the feedback signal or of a series of feedback signals. Atemporary variation of the feedback signal may be indicative of the sizeof the interior volume and/or of the longitudinal position of the bung.

With a further example the processor is connected to the signalgenerator. Typically, the processor is connected to both, the signalgenerator and to the signal receiver. Here, the processor is configuredto trigger the emission of the measurement signal. The processor isfurther configured to determine the size of the interior volume on thebasis of a comparison of at least one measurement signal with at leastone feedback signal. The processor may be further configured to conducta comparison of at least one measurement signal with several feedbacksignals. Alternatively or additionally the processor may be configuredto compare at least one feedback signal with several measurementsignals. Moreover, the processor may be configured to compare amultitude of measurement signals with a multitude of feedback signals.

The signal generator may be configured to emit a series or a sequence ofmeasurement signals. Accordingly, the signal receiver may be configuredto detect a respective series or sequence of measurement signals inreturn. Here, the processor may be configured to conduct a mutualcomparison of feedback signals of a sequence of feedback signals. Inthis way, temporal fluctuations of the feedback signal or of thefeedback signals can be detected. Such a temporal fluctuation may beindicative of the size of the interior volume and/or of the longitudinalposition of the bung relative to the body of the container.

Moreover, since the processor is connected to both, the signal generatorand to the signal receiver the processor may be configured to measure atime delay between the emission of a measurement signal by the signalgenerator and the detection of a feedback signal by the signal receiver.From a determination of such a time delay the size of the interiorvolume and/or the longitudinal position of the bung may be preciselydetermined. In addition or as an alternative, the processor may beconfigured to compare the magnitude or amplitude of the feedback signalwith a given reference amplitude. The amplitude or magnitude of themeasurement signal may be directly indicative of the size of theinterior volume and/or of the longitudinal position of the bung relativeto the body.

In another example the measuring arrangement comprises a data storageconfigured to store at least one of an initial size of the interiorvolume and at least one feedback signal. The data storage may beconfigured to store an initial size of the interior volume or at leastone feedback signal during a calibration procedure of the container. Itis conceivable, that upon or after filling the container with theinjectable medicament the measuring arrangement is triggered to conducta measurement, i.e. to emit a measurement signal and to detect afeedback signal in return.

Such an initial measurement may enable a calibration of the container.In such an initial measurement procedure the interior volume derived bythe processor and/or the feedback signal may be stored as a referencevolume or as a reference signal in the data storage. For subsequentmeasurement procedures the volume derived or determined by the processorand/or the feedback signal obtainable through the signal receiver may becompared to the reference volume and/or to the reference signalpreviously stored in the data storage. The processor may be configuredto conduct a quantitative comparison between a feedback signal and thereference feedback signal previously stored in the data storage. Fromthe size or magnitude of a feedback signal in comparison to the size ormagnitude of the reference feedback signal the size of the interiorvolume and/or the longitudinal position of the bung may be deriveddirectly.

The data storage is typically connected to the processor. It may be alsoconnected to at least one of the signal generator and the signalreceiver. The connection between the processor and the data storageallows for comparing an actually detected feedback signal with apreviously detected feedback signal. The data storage may comprise abuffer for a sequence of feedback signals. The signal receiver may beconfigured to fill the buffer of the data storage as a sequence orseries of feedback signals is detected by the signal receiver. Thebuffer of the data storage and the sequence of feedback signals storedtherein may become subject to a stepwise data processing. The datastorage therefore enables a reduction of the demands to the processor interms of computational power. The electric energy consumption of theprocessor and of the entire measuring arrangement may be decreased bymaking use of the data storage. The data storage is typically integratedinto the integrated circuit of the measuring arrangement. It may belocated on a common PCB of the measuring arrangement. The processor andthe data storage may be located and arranged on a common PCB.

In a further example the container comprises a communication interfaceconfigured to exchange data with an external electronic device. Thecommunication interface may be located inside the bung. It may belong tothe measuring arrangement. Hence, the measuring arrangement may comprisethe communication interface. The communication interface member locatedinside or outside a housing of the measuring arrangement. Thecommunication interface may comprise a wireless communication interface.In a further example the communication interface is a wiredcommunication interface. The communication interface is typicallyconnected to the processor and/or to the data storage. The communicationinterface may be also directly or indirectly connected to at least oneof the signal generator and the signal receiver. The communicationinterface may be connected to both, the signal generator and to thesignal receiver. Typically, the communication interface is locatedinside the bung. The communication interface and the processor areconnected through a wired connection.

In one example, the measuring arrangement may be located or encapsulatedinside the bung while the communication interface is located on anoutside surface of the bung, e.g. on the proximal face of the bung. Thecommunication interface may be also integrated into the measuringarrangement. The communication interface may be located inside thehousing of the measuring arrangement. The communication interface may beintegrated into the integrated circuit of the measuring arrangement. Thecommunication interface, the processor and the storage may be arrangedon a common PCB.

The communication interface is configured to communicate with anexternal electronic device. The communication interface may beconfigured to communicate with the external electronic device inaccordance to a well-defined communication standard or communicationprotocol, such as WIFI, Bluetooth, NFC or other radio frequency-basedcommunication standards. The communication interface may be configuredto exchange data with the external electronic device, such as dataobtained and generated by the processor. The external electronic devicemay be a portable electronic device, such as a smartphone or a tabletcomputer.

The data exchange between the communication interface and the externalelectronic device may comprise unprocessed feedback signals detected bythe signal receiver and transmitted via the communication interface tothe external electronic device. With such an example it is generallyconceivable that it is the external electronic device that comprises aprocessor configured to process feedback signals detected by the signalreceiver and transmitted to the external electronic device via thecommunication interface. In this way, electric power consumption of thecontainer and hence of the measuring arrangement may be reduced.Moreover, the processor can be provided outside and remote from thecontainer. Manufacturing costs for the container and for the measuringarrangement integrated in the bung may be thus reduced.

According to a further example the container comprises an antennaconfigured to withdraw electric energy from a surroundingelectromagnetic field. It may be the measuring arrangement thatcomprises the antenna. The antenna may be arranged in or on the bung ofthe container. Typically, the antenna is electrically connected to theprocessor. The antenna may be further directly electrically connected tothe communication interface. The antenna may be integrated into thecommunication interface or vice versa, i.e. the communication interfacemay be integrated into the antenna. It is conceivable that thecommunication interface communicates with the external electronic devicevia the antenna.

The antenna may therefore provide a twofold functionality. It may enabledata exchange with an external electronic device. Moreover, the antennais configured to withdraw electric energy from a surroundingelectromagnetic field. The antenna may therefore provide and supply themeasuring arrangement with electrical energy obtainable from asurrounding electromagnetic field. The antenna may comprise a NFCantenna. The electric energy necessary to drive or to power themeasuring arrangement may be exclusively provided by the antenna and maybe exclusively withdrawn from a surrounding electromagnetic field.Alternatively or additionally the measuring arrangement may be equippedwith an electric energy storage, such as a battery. In a further examplethe measuring arrangement and hence the bung may be connectable to anexternal source of electric energy. For instance, when assembled insidean injection device the bung may be brought in electrical contact withan electric energy source.

In a further example the measuring arrangement comprises an electricenergy storage that is connected to the antenna. In this way, theantenna is configured to charge the electric energy storage. Insituations where a surrounding electromagnetic field is absent theelectric energy storage may provide sufficient electric energy to driveor to power the measuring arrangement. The electric energy storage istypically connected to the measuring arrangement. It is connected to thesignal generator in order to generate and to emit a measurement signal.

The electric energy storage is also connected to the signal receiver inorder to enable detection of a feedback signal. The electric energystorage is connected to the processor in order to enable a processing ofdetected feedback signals. The electric energy storage may be furtherconnected to the data storage. In this way, reading of data from thestorage as well as writing data into the data storage becomes enabled.The electric energy storage is further connected to the communicationinterface so as to enable data exchange or data transmission to anexternal electronic device.

According to another example the signal generator comprises a lightsource configured to emit an optical measurement signal towards theoutlet. Here, the signal generator may be configured as a light source.The signal generator may comprise a light emitting diode (LED)configured to emit an optical signal, e.g. a light beam or a light pulseof a predetermined frequency or predetermined spectral range or spectralwidth. The optical measurement signal generated and emitted by theoptical signal generator may be in the visible spectrum or in theinvisible spectrum. The optical measurement signal may comprise afrequency in the infrared spectrum or in the ultraviolet spectral range.When the signal generator is configured to generate and to emit anoptical measurement signal in the non-visible range the emission of theoptical measurement signal is not perceivable by users of the container.Hence, the capability and functionality of the measuring arrangement canbe effectively concealed and the user of the container will not bedistracted or confused when the optical signal generator emits anoptical measurement signal.

The optical signal generator may be configured to emit a collimatedlight beam or a collimated light pulse into the interior volume of thecontainer. The measurement signal in form of an optical measurementsignal propagates through at least a portion of the interior volume. Thefeedback signal is also an optical feedback signal. For instance, theoptical measurement signal may be subject to a reflection, e.g. at thesidewall of the body of the container and/or at the outlet. The opticalfeedback signal may be an optical measurement signal reflected by atleast one of the outlet and the sidewall.

The signal receiver typically comprises a light detector, such as acharge coupled light detector. The signal receiver may comprise aphotodiode or a charge coupled device (CCD). The signal receiver may beconfigured to quantitatively determine the magnitude of the opticalfeedback signal. Depending on the transmissivity of the interior volumeand the injectable medicament located therein the decrease in intensityof the optical feedback signal compared to the intensity of the opticalmeasurement signal may be directly indicative of the optical pathlength, the optical measurement signal and the optical feedback signalpropagating through the interior volume.

The attenuation of the intensity of the optical feedback signal comparedto the optical measurement signal may be a direct indication for theoptical path length between the signal generator, a particular portionof the sidewall or the outlet and the signal receiver. As the bung issubject to a distally directed sliding motion the optical path lengthbetween the signal generator and the signal receiver is constantlyreduced thus leading to an increase of the intensity of the opticalfeedback signal. The variations in intensity of the optical feedbacksignal are therefore a direct indication for the longitudinaldisplacement of the bung relative to the sidewall of the container.

With another example the signal receiver comprises a time of flightdetector (TOF) or a TOF camera that is configured to detect the opticalmeasurement signal reflected from the outlet as the optical feedbacksignal. A time of flight detector is configured to measure a timeinterval required for a light pulse to propagate from the signalgenerator towards the outlet and back from the outlet to the signalreceiver. The time of flight measuring depends on the finiteness of thespeed of light and the ability to measure the TOF either directly withclocks or indirectly by, for example, comparing the phase of an emittedlight beam or light pulse with the phase of the reflected light beam orlight pulse.

In another example the signal generator is configured to generate and toemit at least one or several light pulses into the interior volume at afirst point of time t1 and the signal receiver is configured to detectat least one or several reflected light pulses. The signal receiver istypically configured to detect light pulses previously emitted by thesignal generator and reflected by at least one of the sidewall, theoutlet and the proximal surface of the pierceable seal. The signalreceiver is configured to detect or to determine a second point of timet2 at which reflected light pulses are detected. A time interval betweenthe first point of time t1 and the second point of time t2 is indicativeof a time delay required by the emitted light to propagate from thesignal generator to the signal receiver. At least one of the processorand the signal receiver is configured to determine or to measure such atime delay being indicative of the optical path length between thesignal generator and the signal receiver. From this, the distancebetween the bung and an optically reflective structure, e.g. theproximal surface of the pierceable seal, can be precisely determined.Typically, both the signal generator and the signal receiver areconnected to the processor and are driven or triggered by the processor.

With the knowledge of the speed of light of approximately 300,000 km/sthe optical path length between the signal generator, the outlet and thesignal receiver can be precisely determined. The measurement or distanceresolution of the TOF measuring arrangement comprising a TOF sensor maybe less than 1 cm, less than 5 mm or less than 1 mm. The knowledge ofthe relative position of the signal generator and the signal receiverand knowledge of the index of refraction of the interior volume and/orthe injectable medicament located therein allows to derive and toprecisely determine the geometric distance between the bung and theoutlet thus enabling to calculate the size of the interior volume andhence of the momentary filling level of the container.

In one example of operation the optical signal generator and the opticalsignal receiver in its implementation as a time of flight detector areconfigured to generate and to emit several light pulses. As analternative to the measurement of a time delay also a phase shiftbetween the light beams emitted by the optical signal generator and thereflected light beams detected by the optical signal receiver can becompared, e.g. by the processor. The time of flight and hence theoptical path length as well as the geometric path length can then bederived from a phase shift between the emitted light pulses and thedetected light pulses.

With a TOF implementation the processor triggers the optical signalgenerator to emit at least one or a sequence of light pulses propagatinginto and through the interior volume as optical measurement signals.Optical feedback signals provided by a reflection of the opticalmeasurement signals, e.g. at the inside face or proximal face of theoutlet, are detected by the time of flight sensor. The time delaybetween the emission of the optical measurement signal by the signalgenerator and the detection of the optical feedback signal by the signalreceiver is typically measured by a clock

According to a further example the measuring arrangement comprises anoptical interferometer configured to determine a distance between theoutlet and the bung on the basis of an optical phase shift between theoptical feedback signal and a reference optical signal. The opticalinterferometer may be of Mach-Zehnder type or Michelson type. It maycomprise a beam splitter and at least two reflectors, e.g. in form ofmirrors. The optical interferometer typically comprises a reference pathand a signal path. A light beam emitted by a light source is split intoa signal beam and a reference beam.

The reference beam is directed towards a reflector. The distance betweenthe reflector and the respective beam splitter is constant. The signalbeam propagates from the beam splitter to an object. It is reflected bythe object and at least a portion thereof returns to the beam splitter.At the beam splitter, the reference beam reflected from the referencereflector and the signal beam reflected from the object recombine andinterfere. The light source and the light beam emitted by the lightsource comprises a coherence length that is at least half of thedistance of a total axial displacement path of the bung relative to thebody of the container. The optical interferometer may be configured tohave a signal path and a reference path of equal length when the bung isabout halfway between a proximal end position and a distal end position.

As the reflected reference beam and the reflected signal beam arerecombined an interference pattern is generated at the optical signalreceiver. As the bung is subject to a longitudinal movement, thedistance between the beam splitter and the object is subject to avariation thus leading to a quantitative modification of theinterference pattern on the optical signal receiver. The optical signalreceiver typically comprises a charge coupled device. The charge coupleddevice comprises a linear and hence one-dimensional array or atwo-dimensional array of charge coupled detectors or pixels. The patternobtained at the optical signal receiver may be processed by theprocessor. Alternatively, the pattern detected at the optical signalreceiver may be processed by the external electronic device.

For this, the communication interface may be configured to transmit thepattern of the optical signal receiver to the external electronic devicefor further processing. An optical interferometer provides a ratherprecise position and displacement measurement of the bung relative tothe body of the cartridge.

In another example the optical interferometer may be at least partiallyfiber implemented. For instance, the reference path may be provided byan optical fiber. Here, the optical interferometer comprises an opticalfiber forming the reference path for the optical reference signal. Afree end of the optical fiber may comprise a reflective end. Moreover,the fiber can be coiled inside the bung so as to reduce the spacerequired for the measuring arrangement. The optical interferometer maybe configured to direct the signal beam towards the outlet. The outletmay comprise a reflective surface, e.g. in form of a proximal surface ofa pierceable membrane that is provided on the outlet.

Interferometry relies on the wave nature of light and the ability ofwaves to interfere. The signal receiver is typically connected to thesignal generator. Typically, the processor is connected to both, thesignal generator and the signal receiver.

Generally, and for any of the examples as described herein the opticalsignal generator as well as the optical signal receiver can beintegrated on a chip or printed circuit board thus allowing a furtherminiaturization of the size of the measuring arrangement.

When the measuring arrangement is optically implemented, i.e. when thesignal generator is an optical signal generator and when the signalreceiver is an optical signal receiver the bung may comprise atranslucent material. Here, at least one of the optical signal generatorand the optical signal receiver may be located inside the bung at apredetermined non-zero distance from an end face or circumference of thebung. With other examples at least one of the signal generator and thesignal receiver may be located at a distal end face of the bung. Atleast one of the optical signal generator and the optical signalreceiver may flush with the distal face of the bung. In other examplesboth, the signal generator and the signal receiver are located at thedistal end face of the bung or flush with the distal end face of thebung.

According to another example at least one of the optical signalgenerator and the optical signal receiver is arranged in a recess of adistal face of the bung. For instance, the optical signal generator isarranged in the recess. In this way, the propagation characteristics ofthe optical signal generated and emitted by the optical signal generatorcan be influenced. Typically, the optical signal generator is arrangedin a recess of a distal face of the bung while the optical signalreceiver is arranged at the distal face of the bung. Hence, the opticalsignal generator and the optical signal receiver are arranged at apredefined longitudinal offset from each other. The optical signalgenerator and the optical signal receiver may be also offset in radialor circumferential direction. By arranging the optical signal generatorin a recess optical measurement signals emitted by the optical signalgenerator are hindered from impinging the optical signal receiverdirectly. Insofar the recess forms a kind of a screen for the opticalsignal receiver.

In another example it is the optical signal receiver that is arranged ina recess of the distal face of the bung and the optical signal generatoris arranged at the distal face of the bung. In this way, it is theoptical signal receiver that is screened by the recessed arrangement ofone of the optical signal generator and the optical signal receiver atthe distal face of the bung. This provides the benefit that only lightbeams or light pulses reflected from the outlet can be detected by theoptical signal receiver.

The recessed arrangement of at least one of the optical signal generatorand the optical signal receiver in the distal face of the bung is offurther benefit when the bung is positioned rather close to the outletof the container. If the container is almost empty and if the interiorvolume approaches a minimum size the distance between the distal face ofthe bung and the outlet will approach a minimum. With a recessedarrangement of at least one of the optical signal generator and theoptical signal receiver the optical path length between the opticalsignal generator, the outlet and the optical signal receiver can beslightly increased compared to the geometric distance between the outletand the distal face of the bung. This may be beneficial for enabling atime of flight-based distance determination even for small distancesbetween the outlet and the bung.

According to another aspect the disclosure further relates to a methodof determining the size of an interior volume of a container asdescribed above. The method comprises the steps of generating andemitting a measurement signal from the measuring arrangement into orthrough the interior volume of the container. Thereafter, at least onefeedback signal is detected, typically by the signal receiver. Thedetected feedback signal is indicative of an interaction of themeasurement signal with at least one of the sidewall, the outlet or theinterior volume of the container. Thereafter and in a final step thesize of the interior volume is determined on the basis of the feedbacksignal. Typically, the method is conducted by a processor located insidethe bung or provided outside the bung. The processor may be integratedinto the measuring arrangement. With other examples the processor may belocated in an external electronic device. Here, the measuringarrangement may be equipped with a communication interface configured totransmit or to exchange data with the external electronic device. Thecommunication interface is then connected to at least one of the signalgenerator and the signal receiver. It may be connected to both, thesignal generator and the signal receiver.

Generally speaking, the method of determining the size of an interiorvolume of the container is conducted by means of the container asdescribed above. Accordingly, any features, benefits and modes ofoperation described above in connection with the container equally applyto the method of determining the size of the interior volume of thecontainer; and vice versa.

In the present context the term ‘distal’ or ‘distal end’ relates to anend of the injection device that faces towards an injection site of aperson or of an animal. The term ‘proximal’ or ‘proximal end’ relates toan opposite end of the injection device, which is furthest away from aninjection site of a person or of an animal.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

-   -   wherein in one embodiment the pharmaceutically active compound        has a molecular weight up to 1500 Da and/or is a peptide, a        proteine, a polysaccharide, a vaccine, a DNA, a RNA, an enzyme,        an antibody or a fragment thereof, a hormone or an        oligonucleotide, or a mixture of the above-mentioned        pharmaceutically active compound,    -   wherein in a further embodiment the pharmaceutically active        compound is useful for the treatment and/or prophylaxis of        diabetes mellitus or complications associated with diabetes        mellitus such as diabetic retinopathy, thromboembolism disorders        such as deep vein or pulmonary thromboembolism, acute coronary        syndrome (ACS), angina, myocardial infarction, cancer, macular        degeneration, inflammation, hay fever, atherosclerosis and/or        rheumatoid arthritis,    -   wherein in a further embodiment the pharmaceutically active        compound comprises at least one peptide for the treatment and/or        prophylaxis of diabetes mellitus or complications associated        with diabetes mellitus such as diabetic retinopathy,    -   wherein in a further embodiment the pharmaceutically active        compound comprises at least one human insulin or a human insulin        analogue or derivative, glucagon-like peptide (GLP-1) or an        analogue or derivative thereof, or exendin-3 or exendin-4 or an        analogue or derivative of exendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;

Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

-   H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   des Pro36 Exendin-4(1-39),-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group-Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

-   des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),-   H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38 [Trp(02)25] Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,-   H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25]    Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(S1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

It will be further apparent to those skilled in the art that variousmodifications and variations can be made to the present inventionwithout departing from the spirit and scope of the invention. Further,it is to be noted, that any reference numerals used in the appendedclaims are not to be construed as limiting the scope of the invention.

In the following, numerous examples of the container and of an injectiondevice will be described in greater detail by making reference to thedrawings, in which:

BRIEF DESCRIPTION OF FIGURES

FIG. 1 shows an example of an injection device,

FIG. 2 shows the injection device partially disassembled and equippedwith a container filled with an injectable medicament,

FIG. 3 shows a longitudinal cross-section through an example of thecontainer,

FIG. 4 is a block diagram of the measuring arrangement of FIG. 3 ,

FIG. 5 is a further block diagram of an alternative measurementarrangement comprising an optical interferometer,

FIG. 6 shows a flowchart of a method of determining the size of aninterior volume of the container,

FIG. 7 shows a longitudinal cross-section through another example of thecontainer, and

FIG. 8 is illustrative of a further example of a container.

DETAILED DESCRIPTION

In FIGS. 1-2 an example of an injection device 1 configured as a pentype injector is illustrated. The injection device 1 comprises a housing20. The housing 20 comprises a cartridge holder 21 and a body 22. Thecartridge holder 21 is configured to accommodate a container 100 thatmay comprise a cartridge that is prefilled with at least a firstinjectable medicament 50. The cartridge holder 21 and the body 22 may bepermanently or releasably attached to each other. With a permanent ornon-releasable connection of cartridge holder 21 and body 22 theinjection device 1 may be configured as a disposable injection devicewith the container 100 readily assembled therein. Alternatively, theinjection device 1 may be configured as a reusable device. Here, thecartridge holder 21 can be disconnected from the body 22 to replace orto exchange a container 100.

The cartridge holder 21 as illustrated in FIG. 2 comprises a window 25to allow visual inspection of the container 100 located therein. Near adistal end the cartridge holder 21 comprises a socket 31 having an outerthreaded section 32. The socket 31 is configured to support an injectionneedle 40. The injection needle 40 typically comprises a double-tippedhollow cannula having a proximal end and a distal end. The injectionneedle 40 typically comprises a needle hub 41 with an inside threadedportion for releasable connection with the threaded section 132. Theneedle hub 41 comprises a bottom section and a sidewall section forminga cup-shaped receptacle configured to receive the threaded socket 31 ofthe cartridge holder 21. The sidewall section comprises the innerthreaded section that mates with the outer threaded section 32 of thesocket 31. A distal end face of the cartridge holder 21 comprises athrough opening 23 through which the proximally protruding portion ofthe needle 40 can extend into the interior of the cartridge holder 21and hence into the interior of the cartridge or container 100 when theinjection needle 40 is attached to the cartridge holder 21 and when thecontainer 100 is arranged in the cartridge holder 21.

The container 100 is arranged inside the cartridge holder 21. It ispositionally fixed inside the cartridge holder 21. The container 100comprises an elongated and tubular-shaped body 101. The body 101 maycomprise a vitreous body. The body 101 may be made of glass. The body101 may be translucent or transparent in order to allow visualinspection of the content of the container 100. The elongated body 101extends along a longitudinal direction (z). The body 101 comprises thedistal end 103 and an oppositely located proximal end 104.

With the distal end 103 the body 101 is arranged near or at the distalend of the cartridge holder 21. The distal end 103 of the body 101comprises a narrowing shoulder portion 107 extending into a diameterreduced neck portion 105. The radially narrowing shoulder portion 107 isconfigured to abut or to engage axially with a correspondingly-shapedshoulder section of the cartridge holder 21. The shoulder portion 107 islocated close to the distal end 103 of the cartridge or container 100.

At the far distal end the neck portion 105 extends into a radiallywidening head portion 105 a. At the head portion 105 a there is provideda seal 206, e.g. in form of a pierceable sealing disc. This seal 206 maycomprise a pierceable rubber septum that is fixed to the head portion105 a and hence to the distal end 103 of the body 101 by means of aferrule 108 or crimped metal cap. The ferrule 108 may comprise a crimpedaluminium cap. The seal 206 may form or belong to an outlet 109 of thecontainer 100 at the distal end 103 of the elongated body 101.

The injection device 100 may be further equipped with a drive mechanism14 comprising a plunger or a piston rod 11. The drive mechanism 14 maybe further equipped with a trigger 18 by way of which a dispensingaction of the injection device 1 can be triggered or controlled.Optionally, the injection device 1 and the drive mechanism 14 comprise adose dial 16 by way of which a size of a dose to be dispensed can beindividually set or by way of which the injection device 1 can bedeployed or prepared for a subsequent dispensing procedure.

Optionally and as illustrated in FIG. 1 the body 22 of the housing 20may be provided with a dose size indicating window 26. In the window 26the size of a dose actually set can be visually displayed thus informingthe user of the amount of the medicament to be dispensed during asubsequent dispensing procedure.

As further illustrated in FIG. 1 the injection needle 40 may be providedwith an inner needle cap 27 configured to cover the distal end of theinjection needle 40. The injection needle and/or the needle hub 41 maybe further covered by an outer needle cap 28. If not in use theinjection needle 40 should be detached from the distal end of thecartridge holder 21. Then, the cartridge holder 21 can and should becovered by a protective cap 24. The protective cap 124 is configured toreleasably engage with at least one of the cartridge holder 21 and thebody 22. Prior to assemble the injection needle 40 to the cartridgeholder 21 the protective cap 24 has to be detached from the housing 20.

The above described interaction of the container 100 with a pen typeinjection device 1 as illustrated in FIGS. 1-2 is only exemplary. Thegeneral working principle of the container does not require interactionwith a pen type injection device 1. Generally, the container 100 can beimplemented or may be used as a manually operated syringe or as acontainer for an infusion device.

The container 100 as illustrated in FIG. 3 comprises a tubular-shapedelongated body 101 having a tubular-shaped sidewall 102. At the distalend 103 the container 100 comprises an outlet 116. The outlet 116 issealed by the pierceable seal 206. Near a proximal end 104 that isopposite to the distal end 103 the container 100 comprises a bung 210 ora piston. The bung 210 is arranged inside the tubular-shaped sidewall101 of the container 100. The bung 210 is sealingly engaged with aninside section of the sidewall 102. The bung 210 comprises an outertubular shaped sidewall 212 in frictional engagement with an inside ofthe sidewall 102 of the container 100.

The cross-section or diameter of the bung 210 matches with therespective cross-section or diameter of the body 101 and of its sidewall102. The bung 210 comprises a body 211. The bung 210 comprises a distalface 213 facing towards the outlet 116 and hence towards the pierceableseal 206. Opposite to the distal face 213 the bung 210 comprises aproximal face 214. The proximal face 214 serves as a thrust receivingface of the bung 210. The proximal face 214 may get in axial orlongitudinal abutment with the piston rod 11 of the drive mechanism 14of an injection device 1 as illustrated in FIGS. 1 and 2 .

In this way, the bung 210 can be urged or pushed in distal direction 2so as to expel a predefined amount of the injectable medicament 50 froman interior volume 109 of the container 100. The interior volume 109 isconfined in circumferential direction or in radial direction by thesidewall 102 of the container 100. In distal direction 2 the interiorvolume 109 is confined by the outlet 116. The interior volume 109 may beconfined in distal direction 2 by the pierceable seal 206. In proximaldirection 3 the interior volume 109 is confined by the bung 210. Inparticular, the interior volume 109 is confined by the distal face 213of the bung 210.

The interior volume 109 defines the amount of injectable medicament 50accommodated inside the container 100. During use of the container 100and as the injectable medicament 50 is expelled from the interior of thecontainer 100 the size of the interior volume 109 decreases as the bung210 is driven in distal direction 2 towards the outlet 116. In order tomeasure or to determine the size of the interior volume 109 the bung 210comprises a measuring arrangement 220. The measuring arrangement 220 isarranged in or on the bung 210. The measuring arrangement 220 may beencapsulated entirely inside a body 211 of the bung 210. The measuringarrangement 220 may be located inside the bung 210 at a predefinednon-zero distance from any of the distal face 213, the proximal face 214and the outer sidewall 212 of the bung 210.

In one example the measuring arrangement 220 comprises a housing 221.The measuring arrangement 220 or at least one component thereof may bealternatively arranged inside the bung 210 and outside the housing 221so that the measuring arrangement 220 or at least one component thereofis arranged flush with an outer surface of the body 211 of the bung 210.For instance, the measuring arrangement 220 may flush with the distalface 213 or with the proximal face 214. The measuring arrangement 220 orcomponents thereof may also protrude from at least one of the distalface 213 and the proximal face 214.

One example of the measuring arrangement 220 with its components isschematically illustrated in more detail in FIG. 4 . The measuringarrangement 220 comprises a signal generator 222 that is configured toemit an electromagnetic measurement signal S1 into or through theinterior volume 109. The measurement signal S1 is an electromagneticsignal. The electromagnetic signal may comprise or represent an opticalsignal. It may comprise at least one of a light beam and a light pulse.

The measuring arrangement 220 further comprises a signal receiver 224that is configured to detect an electromagnetic feedback signal F1. Theelectromagnetic feedback signal F1 is indicative of an interaction ofthe measurement signal with at least one of the sidewall 102, the outlet116 and the interior volume 109. By emitting the measurement signal S1into the interior volume 109 a respective feedback signal F1 isgenerated that is directly indicative of the interaction of themeasurement signal S1 with at least one of the sidewall 102, the outlet116, the pierceable seal 206 or the interior volume 109. On the basis ofthe detected feedback signal F1 alone or on the basis of a comparison ofthe feedback signal F1 with the measurement signal S1 a precisedetermination of the size of the interior volume 109 can be provided.Based on the feedback signal F1 alone and/or based on the respectivemeasurement signal S1 the longitudinal position of the bung 210 relativeto the body 101 of the container 100 can be determined or measured. Fromthis, a momentary size of the interior volume 109 can be derived.

The block diagram of FIG. 4 shows one example of a measuring arrangement220. The measuring arrangement 220 may comprise a housing 221 thatprovides and enables an encapsulation of the measuring arrangement 220in the inside of the body 211 of the bung 210. The measuring arrangement220 comprises a processor 226. The processor 226 is a microprocessor,e.g. in form of a microcontroller or in form of an application-specificintegrated circuit (ASIC). The measuring arrangement 220 may comprise aPCB 229. In the example of FIG. 4 the signal generator 222 of themeasuring arrangement 220 comprises a light source 240, such as a lightemitting diode (LED).

Upon manufacturing, assembly or filling of the container 100 with theinjectable medicament 50 a measureable geometric property of thecontainer 100 can be individually determined.

The measuring arrangement 220 may further comprise a communicationinterface 230 that is configured to exchange data with an externalelectronic device 400 as illustrated in FIG. 2 . The external electronicdevice 400 typically comprises a processor 402, a data storage 404 and acommunication interface 406. The communication interface 406 isconfigured to communicate and to exchange data with the communicationinterface 230 of the measuring arrangement 220. Typically, thecommunication interface 230 as well as the communication interface 406is or are configured for wireless data transmission. The communicationinterface 230 and/or the communication interface 406 might be configuredto communicate via RF electromagnetic signals. The communicationinterfaces 230, 406 may be for instance configured for wirelesscommunication in accordance to the Wi-Fi standard (IEEE802.11), RFID orNFC communication or Bluetooth communication protocols and standards.

The measuring arrangement 220 may further comprise an antenna 234 inorder to enable wireless data transmission between the measuringarrangement 220 and an external electronic device 400. The antenna 234may be further configured to withdraw or to harvest electromagneticenergy from an external electromagnetic field EM, e.g. from aradio-frequency field (RF). It is generally conceivable, that themeasuring arrangement 220 is entirely driven by electromagnetic energywithdrawn from an external electromagnetic field EM. Alternatively oradditionally it is conceivable that the measuring arrangement 220comprises an electric energy storage 238, e.g. implemented as arechargeable battery. The electric energy storage 238 may be connectedto the antenna 234 as well as to the processor 226. The electric energystorage 238 can be recharged by electric energy withdrawn from theexternal electromagnetic field EM through the antenna 234.

It is generally conceivable, that the processor 226 is limited totransfer electric signals obtainable from a signal receiver 224 via thecommunication interface 230 to the external electronic device 400. Inthis way, computational power of the measuring arrangement 220 as wellas electric power consumption could be reduced to a minimum. Theprocessing of signals obtainable from the signal receiver 224 may beentirely conducted by the processor 402 of the external electronicdevice 400. Hence, a software application implemented in the externalelectronic device 400 may provide a calculation of the size of theinterior volume 109 and may be configured to determine the momentaryfilling level of the container 100.

With another example the processor 226 may be configured to determine orto calculate the size of the interior volume 109 based on the signalsreceived by the signal receiver 224. Pre-processed signals orunprocessed signals of the receiver 224 and/or processed data derivedfrom a detected feedback signal and/or from an emitted measurementsignal may be also stored in the data storage 228. Communication andtransfer of data between the measuring arrangement 220 and the externalelectronic device 400 may be thus limited to the size of the interiorvolume and/or to the momentary longitudinal position of the bung 210relative to the body 101 of the container 100.

Furthermore, it is conceivable, that the data storage 228 is configuredto store numerous size informations regarding the interior volume orregarding the longitudinal position of the bung 210. The data storage228 may be configured to store a dosing history. The data storage 228may be configured to store data derived from the measurement signal S1and/or from the feedback signal F1 together with a timestamp. In thisway a dosing history of the container 100 may be stored inside the bung210.

The signal generator 222 of the example according to FIGS. 3 and 4 isconfigured to emit an optical, hence an electromagnetic measurementsignal S1. The electromagnetic measurement signal S1 is generated andemitted by the signal generator 222 in such a way that the opticalmeasurement signal S1 propagates into the interior volume 109 of thecontainer 100. The optical measurement signal S1 is interacting with atleast one of the sidewall 102, the outlet 116 or the interior volume109, hence with the injectable medicament 50. The optical measurementsignal S1 may be reflected, diffracted, and/or absorbed by at least oneof the sidewall 102, the outlet 116, the interior volume 109 and theinjectable medicament 50 located therein. In reaction to suchinteraction there is generated or there emerges an electromagneticfeedback signal F1 that is detectable by the signal receiver 224.

In one example the signal generator 222 comprises a light source 240 toemit a light beam or a light pulse into the interior volume 109. Thesignal receiver 224 may comprise a photodiode or a light detector, e.g.in form of a charge coupled device to detect the optical feedback signalF1. In one example the signal receiver comprises an opticalTime-of-flight (TOF) detector 242. The optical feedback signal F1 may bea reflection of the optical measurement signal S1. As an alternative itmay be a portion of the optical measurement signal S1 scattered on or byat least one of the sidewall 102, the outlet 116, the interior volume109 or the injectable medicament 50.

In one example the signal receiver 224 is a time of flight detector 242.For this, both the signal generator 222, e.g. in form of an ultra-fastLED and the signal receiver 224 are connected to the processor 226. Thesignal generator 222 may be pulsed by a comparatively fast currentsource 223 controlled and triggered by the processor 226. The signalreceiver 224, e.g. in form of an extremely or comparatively fast TOFsensor or photodiode receives the electromagnetic or optical feedbacksignals F1 that are reflected from the interior volume 109, from theoutlet 116 or from the sidewall 102 of the body 101 of the container.Typically, several light pulses or a sequence of light pulses isgenerated and emitted by the signal generator 222.

The detected reflected light pulses forming the optical feedback signalF1 are detected by the signal receiver 224. From a phase shift and/orfrom a time delay between the emission of optical measurement signals S1and the detection of respective optical feedback signals F1 theprocessor 226 is able to calculate or to determine a runtime or adistance between the signal generator 222, a reflected structure of thecontainer and the signal receiver 224. Typically, an inside surface 207or the proximal surface of the pierceable seal 206 may comprise areflective surface. In this way, optical measurement signals S1propagating through the interior volume 109 are reflected at theproximal surface 207 and are returned as optical feedback signals F1 tothe signal receiver 224. Also here and upon manufacturing, upon assemblyor upon filling of the container 100 a respective calibration proceduremay be conducted.

For instance, the signal generator 222 is configured to generate and toemit at least one or several light pulses into the interior volume 109at a first point of time t1 and the signal receiver 224 is configured todetect at least one or several reflected light pulses. The signalreceiver 224 is particularly configured to detect light pulsespreviously emitted by the signal generator 222 and reflected by at leastone of the sidewall 102, the outlet 116 and the proximal surface 207 ofthe pierceable seal 206. The signal receiver 224 is configured to detector to determine a second point of time t2 at which reflected lightpulses are detected. A time interval between the first point of time t1and the second point of time t2 is indicative of a time delay requiredby the emitted light to propagate from the signal generator 224 to thesignal receiver 224. Typically, both the signal generator 222 and thesignal receiver 224 are connected to the processor 226 and are driven ortriggered by the processor 226. The optical signal generator 222 and/orthe optical signal receiver 224 may be entirely enclosed or embeddedinside the body 211 of the bung 210. For this the material of the body211 of the bung 210 may be substantially translucent for the wavelengthof the electromagnetic measurement signal and the respectiveelectromagnetic feedback signal. Otherwise and with a non-translucent ornon-transparent material of the bung 210 the optical signal generator222 and the optical signal receiver 224 may be located at the distalface 213 of the body 211 of the bung 210.

As illustrated in FIG. 3 at least one of the signal generator 222 andthe signal receiver 224 may be located in a recess 215 of the distalface 213 of the bung 210. As illustrated in FIG. 3 , the signalgenerator 222, e.g. in form of an LED is located in the recess 215. Theoptical signal receiver 224 is flush with the distal face 213 of thebody 211 of the bung 210. In this way it is guaranteed that even in adistal most position of the bung 110 there remains at least a minimumpropagation distance for the optical measurement signal S1 and theoptical feedback signal F1 which is required to enable a measurement ofthe distance between the bung 210 and the outlet 116.

The recessed arrangement of the optical signal generator 222 is alsobeneficial to avoid a direct illumination of the optical signal receiver224 by electromagnetic or optical measurement signals S1. The recessedarrangement of at least one of the signal generator 222 and the signalreceiver 224 provides a kind of a screening for the optical signalreceiver 224. In this way it can be provided that only optical feedbacksignals F1 reflected from at least one of the sidewall 102, the outlet116 or the proximal surface 207 impinge on the signal receiver 224.

In another example as indicated in FIG. 5 the measuring arrangement 320comprises an optical interferometer 321. The optical interferometer 321comprises an optical signal generator 322 comprising a light source 340,e.g. an LED configured to generate a light beam or a light pulse of asufficient coherence length. The optical interferometer 321 furthercomprises a processor 326 and an optical signal receiver 324. Theoptical signal receiver may comprise a photodiode or an array ofphotodiodes or charge coupled pixels.

The optical interferometer 321 is embedded inside the bung 210 asillustrated in FIG. 3 . The optical interferometer 321 comprises a beamsplitter 327 and a reflector 228. A light beam produced by the opticalsignal generator 322 propagates to the beam splitter 327. There, thelight beam is split into a signal beam S2 and into a reference beam RS.The reference beam RS is reflected towards the reflector 328. At thereflector 328 the reference beam RS is reflected towards the beamsplitter 327. The signal beam S2 representing the optical measurementsignal propagates into the interior volume 109 of the container 100.There, it is reflected at a reflective structure, e.g. at the insidesurface 207 of the pierceable seal 206. In one example the beam splitter327, the optical signal receiver 224 and the reflector 328 are allimplemented and arranged inside the bung 210.

The beam splitter 327 may be arranged in the distal face 213 of the bung210. It may be arranged in a recess 215 of the distal face 213 asdescribed in connection with FIG. 3 . The optical feedback signal F2reflected from the surface 207 is redirected towards the beam splitter327. There, the reflected reference beam RS and the optical feedbacksignal F2 recombine and co-propagate towards the optical signal receiver324. As a consequence, an interference pattern evolves on the opticalsignal receiver 324. As the distance between the beam splitter 327 andthe surface 207 changes because of a movement of the bung 210 towardsthe outlet 116 the structure of the interference pattern changes. Thechange of the structure of the interference pattern is directlyindicative of the distance the bung 210 is displaced relative to thebody 101 of the container 100.

The distance between the beam splitter 327 and the reflector 328 isconstant. The reference beam RS may propagate through an optical fiber329 also enabling to realize a comparatively long optical path lengthbetween the beam splitter 327 and the reflector 328 inside the bung 210.

In the flowchart of FIG. 6 various method steps of the method ofdetermining the size of the interior volume 109 are illustrated. In aninitial step 500 the container 100 is assembled. Here, the bung 210 isinserted into the body 101 of the container 100. Thereafter the outlet116 may be sealed, e.g. by arranging the pierceable seal 206 on the headportion 105 a of the container 100. In a subsequent step 502 an initialmeasurement is conducted. Here, the signal generator 222, 322 istriggered to emit at least one measurement signal S1, S2 into or throughthe interior volume 109. At least one or a sequence of feedback signalsF1, F2 is or are detected by the signal receiver 224, 324. Thereafter ina subsequent step 504, the measured signals are calibrated. Hence, theresults of the initial measurement are assigned with the actual size ofthe interior volume 109 that is determined or predetermined during theassembly process.

In step 506 a calibration is stored in the data storage 228. Later onand during use of the container, e.g. in an injection device themeasuring arrangement 220, 320 may be triggered to conduct a respectivemeasurement and to emit at least a measurement signal S1, S2 into orthrough the interior volume 109 in step 508.

In a subsequent step 510 at least one or a series of feedback signalsF1, F2 is or are received by the signal receiver 224, 324. From thereceived signal(s), in particular from a time delay between submissionof the electromagnetic measurement signal and receiving of a reflectedelectromagnetic feedback signal and with knowledge of the refractiveindex of the medium through which the electromagnetic signals propagatean optical path length between the signal generator and the signalreceiver can be calculated on the basis of the known velocity of theelectromagnetic radiation. From the time delay an axial distance betweenthe distal face 213 of the bung 210 and e.g. the proximal surface 207 ofthe pierceable seal 206 can be calculated in step 512. Having knowledgeof the diameter and/or of the geometric cross-section of the container100 the size of the interior volume 209 and the amount of medicamentleft inside the container 100 can be precisely calculated.

It should be noted, that various modifications to the flowchart asdescribed above with respect to FIG. 6 are conceivable in accordance tothe functionality of the various examples of the measuring arrangementand its interaction with, e.g. an external electronic device 400.

Two further examples of drug containers 100 are illustrated in FIG. 7and FIG. 8 . There, the bung 210 comprises a rather large recessedportion 215. A distal face 213 of the bung 210 is in contact with theliquid drug 50. The recessed portion 215 is open towards the interiorvolume 109. As illustrated in FIG. 7 the signal receiver 224 is locatedon a bottom of the recessed portion 215. The axial length of therecessed portion 215 is larger than 30% of the total axial length L ofthe bung 210. It may be larger than 50% of the total axial length L ofthe bung 210. In other examples, the axial length or axial depth of therecessed portion 215 may be larger than 60%, larger than 75% or evenlarger than or equal to 80% of the total axial length L of the bung 210.

In this way the optical path length for electromagnetic radiationemitted by the signal generator, reflected at the distal end 103 anddetected by the signal receiver 224 can be substantially prolongedcompared to the example as illustrated in FIG. 3 . This is of particularbenefit when the bung 210 should be located rather close to the distalend 103 of the container 100. The prolongation of the optical pathlength is beneficial for a time-of-flight measurement of electromagneticradiation emitted by the signal generator 222 and received through thesignal receiver 224. The axial length of the recessed portion 215provides a well-defined runtime offset for at least one of theelectromagnetic signals S1, F1.

Apart from this geometric variation the bung 210 of FIG. 7 is ratheridentical or highly similar to the bung 210 as described with regard toFIG. 3 . Insofar all features and properties of the bung 210 asdescribed in connection with FIG. 3 are equally valid for the bung 210as described in FIGS. 7 and 8 .

As an alternative to the illustration of FIG. 7 the recessed portion 215may accommodate the signal generator 222, whereas the signal receiver224 is located at the distal face 213 of the bung 210. At least one ofthe signal generator 222 and the signal receiver 224 is located on thebottom of the recessed portion 215.

With the example of FIG. 8 the recessed portion 215 is divided into afirst recessed section 215 a and a second recessed section 215 b. In thefirst recessed section 215 a there is located the signal receiver 224.In the second recessed section 215 b there is located the signalgenerator 222. The two recessed portions 215 a, 215 b are separated by aseparator 216. The separator 216 may be formed by a partition wallprotruding axially in distal direction from a bottom of the recessedportion 215. The first recessed section 215 a and the second recessedsection 215 b are separated in radial direction. They may be located atthe same or at different axial positions with regard to the axialelongation of the bung 210.

Also here, the total axial length of the recessed portion 215 can belarger than 30%, larger than 50%, of the land 60%, larger than 75% oreven larger than or equal to 80% of the total axial length L of the bung210. The axial length of the separator 216 may be smaller than the axiallength of the recessed portion 215. Insofar, a free and distallyextending end of the separator 216 facing away from the bottom of therecessed portion 215 may be proximally recessed compared to the distalface 213 of the bung 210. With other examples the total axial length ofthe separated 260 may be substantially equal to the axial length of therecessed portion 215 or of any of its recessed sections 215 a, 215 b.

With any of the examples as illustrated in the figures and/or asdescribed above the recessed portion 215 may be either filled by theliquid medicament 50 or it may be filled with a transparent fillingmaterial 217. For instance, the recessed portion 215 may be filled witha transparent polymer. The filling material 217 may comprise at leastone of COC, PA, PP, PE, POM, PS, ABS, COP or mixtures thereof. Fillingthe recessed portion 215 by a filling material 217 is beneficial tomaintain the mechanical stability of the bung 210 and to provide asufficient sealing functionality of the bung 210 with regard to thesidewall 212.

LIST OF REFERENCE NUMBERS

-   -   1 injection device    -   2 distal direction    -   3 proximal direction    -   11 piston rod    -   14 drive mechanism    -   16 dose dial    -   18 trigger    -   20 housing    -   21 cartridge holder    -   22 body    -   23 through opening    -   24 cap    -   25 window    -   26 window    -   27 inner needle cap    -   28 outer needle cap    -   31 socket    -   32 thread    -   40 injection needle    -   41 needle hub    -   50 medicament    -   100 container    -   101 body    -   102 sidewall    -   103 distal end    -   104 proximal end    -   105 neck portion    -   105 a head portion    -   107 shoulder portion    -   108 ferrule    -   109 interior volume    -   115 sidewall    -   116 outlet    -   206 pierceable seal    -   207 surface    -   209 interior volume    -   210 bung    -   211 body    -   212 sidewall    -   213 distal face    -   214 proximal face    -   215 recessed portion    -   215 a recessed section    -   215 b recessed section    -   216 separator    -   217 filling material    -   220 measuring arrangement    -   221 housing    -   222 signal generator    -   223 current source    -   224 signal receiver    -   226 processor    -   228 data storage    -   229 printed circuit board    -   230 communication interface    -   234 antenna    -   238 electric energy storage    -   240 light source    -   242 TOF detector    -   320 measuring arrangement    -   321 optical interferometer    -   322 signal generator    -   324 signal receiver    -   326 processor    -   327 beam splitter    -   328 reflector    -   329 optical fiber    -   340 light source    -   400 external electronic device    -   402 processor    -   404 data storage    -   406 communication interface

1.-15. (canceled)
 16. A drug delivery device comprising: a medicamentcontainer containing a medicament; a bung configured to slide within themedicament container for dispensing the medicament, the bung comprisinga recess defined by a sidewall that extends from a distal surface of thebung to a proximal surface of the recess; a transmitter configured totransmit a first signal in a distal direction within the medicamentcontainer such that the first signal reflects off of at least onesurface of the medicament container; a receiver configured to receive areflected portion of the first signal after the first signal hasreflected off of the at least one surface of the medicament container;and a processor configured to determine an axial position of the bungbased on the reflected portion of the first signal, wherein at least oneof the transmitter or the receiver is disposed in the recess of thebung.
 17. The drug delivery device of claim 16, wherein an axial lengthof the recess is at least 30% of an overall axial length of the bung.18. The drug delivery device of claim 16, wherein the proximal surfaceof the recess comprises a distally-extending protrusion.
 19. The drugdelivery device of claim 18, wherein the distally-extending protrusionis configured to shield or screen the receiver from the transmitter. 20.The drug delivery device of claim 18, wherein the transmitter and thereceiver are disposed in the recess of the bung.
 21. The drug deliverydevice of claim 16, wherein the recess is a first recess, the sidewallis a first sidewall, and the distal surface of the bung comprises asecond recess defined by a second sidewall that extends from the distalsurface of the bung to a proximal surface of the second recess.
 22. Thedrug delivery device of claim 21, wherein an axial length of the firstrecess is different from an axial length of the second recess.
 23. Thedrug delivery device of claim 16, wherein the distal surface of the bungis in contact with the medicament and the proximal surface of the bungis configured to receive a force from a piston rod of the drug deliverydevice.
 24. The drug delivery device of claim 16, wherein a neck portionof the medicament container is configured to engage a shoulder portionof a container holder of the drug delivery device to limit distalmovement of the medicament container relative to the container holder.25. The drug delivery device of claim 16, wherein a dose dial of thedrug delivery device is rotatable relative to a longitudinal axis of thedrug delivery device to set a dosage of the medicament.
 26. A bung for amedicament container, the bung comprising: a recess defined by asidewall that extends from a distal surface of the bung to a proximalsurface of the recess; a transmitter configured to transmit a firstsignal in a distal direction within the medicament container such thatthe first signal reflects off of at least one surface of the medicamentcontainer; and a receiver configured to receive a reflected portion ofthe first signal after the first signal reflects off of the at least onesurface of the medicament container, wherein at least one of thetransmitter or the receiver is disposed in the recess of the bung. 27.The bung of claim 26, wherein an axial length of the recess is between30% and 80% of an overall axial length of the bung.
 28. The bung ofclaim 27, wherein the axial length of the recess is between 50% and 60%of the overall axial length of the bung.
 29. The bung of claim 26,wherein the transmitter is axially offset from the receiver.
 30. Thebung of claim 26, wherein at least one of the transmitter or thereceiver is flush with the distal surface of the bung.
 31. The bung ofclaim 26, wherein at least one of the transmitter or the receiver isdisposed at the proximal surface of the recess of the bung.
 32. The bungof claim 26, wherein at least a portion of the recess has a diameterthat varies along an axial direction of the bung.
 33. The bung of claim32, wherein the diameter of the recess decreases along a proximaldirection of the bung.
 34. The bung of claim 26, wherein the recess is afirst recess, the sidewall is a first sidewall, and the distal surfaceof the bung comprises a second recess defined by a second sidewall thatextends from the distal surface of the bung to a proximal surface of thesecond recess.
 35. The bung of claim 26, wherein the proximal surface ofthe recess comprises a distally-extending protrusion configured toshield or screen the receiver from the transmitter.